4.2 Article

Transcriptional Profile of HCV Replicon Cells after Treatment with Acetylsalicylic Acid

Journal

ANNALS OF CLINICAL AND LABORATORY SCIENCE
Volume 52, Issue 2, Pages 222-229

Publisher

ASSOC CLINICAL SCIENTISTS

Keywords

HCV; ASA; cDNA-microarray; biomarkers; hepatocarcinoma

Funding

  1. CONACyT

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This study demonstrated that acetylsalicylic acid (ASA) regulates the expression of non-structural hepatitis C virus (HCV) proteins in hepatocellular carcinoma cells. ASA can modulate the expression of genes with oxidative roles, with IL-8, CYP450, and MTs genes upregulated and RRs genes downregulated. This suggests that ASA may interfere with HCV replication by altering the antioxidant microenvironment.
Objective. It has been demonstrated in vitro that acetylsalicylic acid (ASA) treatment halves hepatitis C virus (HCV) expression in hepatocarcinoma cells. However, the signaling pathway that promotes this ASA-induced antiviral effect has not yet been identified. Aim. The aim of this work was to identify alterations in the transcriptional profile of Huh-7-HCV-subgenomic replicon cells with vs. without ASA treatment. This comparison sheds light onto the signaling pathways and molecular mechanisms involved in the antiviral effects of ASA. Methods. Human hepatocellular carcinoma (Huh-7) cells that express nonstructural HCV proteins (Huh-7-HCV-replicon cells) were exposed to 4 mM ASA for 0, 24, 48, and 72 hours. Total RNA was isolated, and cDNA was synthesized. Transcripts were then tagged with biotin and purified. Thereafter, they were fragmented and hybridized on HG-U133 Plus 2 Gene Expression chips. Hybridization signals were captured using a GeneChip 3000 7G Scanner and analyzed via Expression Console and dChip Software. Results. When exposed to ASA, hepatocarcinoma cells with non-structural HCV proteins were found to differentially regulate genes with oxidative roles in the cell. The most upregulated genes were interleukin 8 (IL-8), cytochrome P450 (CYP450), and metallothioneins (MTs), while the most downregulated genes were ribonucleotide reductases (RRs). Conclusion. These results show that ASA modulates the expression of genes with antioxidant functions. This suggests that ASA induces a remodeling of the antioxidant microenvironment, which may in turn interfere with the replication of HCV.

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